Sorafenib-loaded PAMAM dendrimer attenuates liver fibrosis and its complications in bile-duct-ligated rats

2019 ◽  
Vol 97 (8) ◽  
pp. 691-698
Author(s):  
Fatemeh Shafie ◽  
Fatemeh Nabavizadeh ◽  
Mehdi Shafie Ardestani ◽  
Mahshid Panahi ◽  
Soheila Adeli ◽  
...  

We assessed the effect of sorafenib-loaded polyamidoamine (PAMAM) dendrimer on liver fibrosis induced by bile duct ligation (BDL). Male Wistar rats were divided into 9 groups: intact, sham, DMSO + BDL, BDL, sorafenib (30 mg/kg), sorafenib (60 mg/kg), PAMAM + BDL, sorafenib (30 mg/kg) + PAMAM + BDL, sorafenib (60 mg/kg) + PAMAM + BDL. BDL was induced and then rats were treated daily with sorafenib and (or) PAMAM for 4 weeks. Improvement of liver was detected via assessment of ascites formation, collagen deposition, liver blood flow, vascular endothelial growth factor level, and blood cells count. Sorafenib-loaded PAMAM dendrimer in both 30 and 60 mg/kg doses reduced ascites formation, reduced collagen deposition, and improved drug-induced hematological side effects of sorafenib alone in comparison with sorafenib-alone treatment. Sorafenib-loaded PAMAM dendrimer increased liver blood flow compared with sorafenib-received groups. Sorafenib-loaded PAMAM dendrimer reduced BDL-induced liver injury compared with sorafenib-received groups. Moreover, sorafenib-loaded PAMAM dendrimer decreased vascular endothelial growth factor level in serum and liver tissue in comparison with sorafenib-received groups. Sorafenib-loaded PAMAM dendrimer profoundly improved the therapeutic effects of sorafenib in BDL rats.

CHEST Journal ◽  
2000 ◽  
Vol 118 (6) ◽  
pp. 1747-1753 ◽  
Author(s):  
Dong-sheng Cheng ◽  
Y. C. Gary Lee ◽  
Jeffrey T. Rogers ◽  
Elizabeth A. Perkett ◽  
J. Philip Moyers ◽  
...  

2018 ◽  
Vol 4 (1) ◽  
pp. 71-76 ◽  
Author(s):  
Antonietta Gigante ◽  
Luca Navarini ◽  
Domenico Margiotta ◽  
Biagio Barbano ◽  
Antonella Afeltra ◽  
...  

Introduction: Since female sexual dysfunction in systemic sclerosis women is multifactorial, we can assume that vascular damage may play a role in pathogenesis. The aim of the study was to evaluate the clitoral blood flow, by Echo color Doppler, and to correlate it whit serum levels of vascular endothelial growth factor and endostatin. Methods: A total of 15 systemic sclerosis women and 10 healthy controls matched for sex and age were enrolled in this study. Serum VEGF165 and endostatin levels were determined in systemic sclerosis patients by commercial enzyme-linked immunosorbent assay kit. Clitoral blood flow was measured by Doppler indices of clitoral artery: pulsatile index, resistive index, and systolic/diastolic ratio were measured. Sexual dysfunction was assessed by Female Sexual Function Index. Results: Vascular endothelial growth factor (pg/mL) and endostatin (ng/mL) median values were significantly higher in systemic sclerosis women than healthy controls. Resistive index and systolic/diastolic ratio median values were significantly higher in systemic sclerosis women than healthy controls. Negative correlation exists between serum levels of vascular endothelial growth factor and resistive index (r = −0.55, p < 0.05). Positive correlation was observed between serum levels of endostatin and resistive index (r = 0.70, p < 0.01) and systolic/diastolic ratio (r = 0.77, p < 0.01). Discussion: We can suppose that clitoral blood flow in systemic sclerosis women is reduced not only for macro- and microvascular damage but also for impaired angiogenesis.


CHEST Journal ◽  
2006 ◽  
Vol 129 (2) ◽  
pp. 407-411 ◽  
Author(s):  
Hideo Mitsuyama ◽  
Wataru Matsuyama ◽  
Jun Iwakawa ◽  
Ikkou Higashimoto ◽  
Masaki Watanabe ◽  
...  

2019 ◽  
Vol 02 (02) ◽  
pp. 107-107 ◽  
Author(s):  
Margalef R. ◽  
Minaya Muñoz F. ◽  
Valera Garrido F. ◽  
Santafe MM

Abstract Background The action of galvanic currents (GC) includes the generation of vasoactive substances such as, for example the vascular endothelial growth factor (VEGF) and its receptor, VEGFR-2. Aim To evaluate modifications in blood flow by action of the galvanic current. Material and Methods The experiments have been performed in Swiss male mice (45-50 days old). The experiments were performed at controlled temperature and light settings. The hypodermis of the skin in the cranial area was used. The procedures were as follows: 1) A portion of skin was sectioned and lifted to obtain a control image; 2) the needle (Physio Invasiva 0.30 × 40mm) was placed over the surface of the skull and covered with skin; 3) treatment was applied using 3 mA, during 3 seconds and three applications (Physio Invasiva Prim); 4) the skin was immediately lifted once again and 3h later to obtain experimental images. In the case of the controls, process 1-4 was repeated, however without applying current. The images were binarized (Digimizer 4.6.1. MedCalc Software) and the area occupied by the vessels of the same surface for each image. Results In mice treated using the GC protocol 3mA, 3 seconds and 3 applications, an increase of 38.53% ± 0.006 was obtained immediately after the application of the GC. However, at three hours, this variation disappears (% of variation: 4.03 ± 0.01), recovering control values. In the control experiments there was no modification. Conclusions Galvanic currents provoke an immediate and transitory vasodilation in mid to small caliber vessels. An immediate and transitory vasodilation has two consequences: the arrival of cells responsible for the inflammatory reaction is accelerated (an essential and necessary step for the regeneration of tissues) and lavage of nociceptive substances is facilitated, which supports an analgesic effect.


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